Tyrosine-specific protein kinase is an enzyme activity associated with several oncogene proteins and growth factor receptors. Proteins with this rare activity have been shown to cause tumors in animals and to be amplified in some human tumors. Our preliminary studies indicate that serum is an easily obtained human specimen which can be used to investigate tyrosyl kinases expressed in normal and neoplastic cells in the intact organism. We have found that serum tyrosyl kinase activity is developmentally expressed in humans and that the activity is elevated in sera from some patients with neoplastic disorders. Our aims are: (1)\to identify serum tyrosyl kinases that may be associated with human neoplastic disorders; (2)\to identify serum tyrosyl kinases that may be used in cancer diagnostic tests; and (3)\to identify tyrosyl kinases that are associated and different stages of human development. To achieve these aims we will fractionate and characterize the different tyrosyl kinase species in human serum. The relationship of serum enzymes with growth factor receptors and oncogene proteins will be established by biochemical comparisons and by reactivity to specific immunological reagents. Those serum tyrosyl kinases that are unrelated to previously identified enzymes will be autophosphorylated to identify the active subunit molecular weights, tested for glycosylation, and used to prepare antibodies. Comparisons will be made of the specific tyrosyl kinases and their levels of activity in sera from different age groups to define the species that are developmentally expressed and in sera from patients with different neoplastic disorders to define the species that are associated with neoplasia. Correlations of the levels of the enzyme with the stage of the disease will indicate the value of the tyrosyl kinase assay in cancer diagnosis. (1)